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Biomedical subjects

E Peterhans

Publications and source records attributed to E Peterhans.

At least 19 recordsLinked to original sources
PubMed2006

[How the bovine viral diarrhea virus outwits the immune system].

The interaction of bovine viral diarrhea virus (BVD virus) with its host has several unique features, most notably the capacity to infect its host either transiently or persistently. The transient infection stimulates an antiviral immune reaction similar to that seen in other transient viral infections. In contrast, being associated with immunotolerance specific for the infecting BVD viral strain, the persistent infection differs fundamentally from other persistent infections like those caused by lentiviruses. Whereas the latter are characterized by complex viral evasion of the host's adaptive immune response by mechanisms such as antigenic drift and interference with presentation of T cell epitopes, BVD virus avoids the immune response altogether by inducing both humoral and cellular immune tolerance. This is made possible by invasion of the fetus at an early stage of development. In addition to adaptive immunity, BVD virus also manipulates key elements of the host's innate immune response. The non-cytopathic biotype of BVD virus, which is capable of persistently infecting its host, fails to induce type I interferon. In addition, persistently infected cells are resistant to the induction of apoptosis by double-stranded RNA and do not produce interferon when treated with this pathogen-associated molecular pattern (PAMP) that signals viral infection. Moreover, when treated with interferon, cells persistently infected with non-cytopathic BVD virus do not clear the virus. Surprisingly, however, despite this lack of effect on persistent infection, interferon readily induces an antiviral state in these cells, as shown by the protection against infection by unrelated viruses. Overall, BVD virus manipulates the host's interferon defense in a manner that optimises its chances of maintaining the persistent infection as well as decreasing the risks that heterologous viral infections may carry for the host. Thus, since not all potential host cells are infected in animals persistently infected with BVD virus, heterologous viruses replicating in cells uninfected with BVD virus will still trigger production of interferon. Interferon produced by such cells will curtail the replication of heterologous viruses only, be that in cells already infected with BVD virus, or in cells in which the heterologous virus may replicate alone. From an evolutionary viewpoint, this strategy clearly enhances the chances of transmission of BVD virus to new hosts, as it attenuates the negative effects that a global immunosuppression would have on the survival of persistently infected animals.

Animals↗
PubMed2005

Genetic heterogeneity of pestiviruses of ruminants in Switzerland.

We have genetically analyzed ruminant pestiviruses. All >150 bovine viral diarrhea (BVD) viruses isolated from cattle in Switzerland belonged to genotype 1, with subgenogroups e, h, k and b found in decreasing frequency. To date, representatives of subgenogroup k have been detected in Switzerland only. Despite serological evidence of Border disease in sheep, only few Border disease viruses have been isolated, all of which belong to the novel group 3. Serological evidence suggested that pestivirus infections may occur also in wild ruminants in Switzerland but no isolates are available for analysis. In addition, we describe two pestiviruses, one a cell culture contaminant and the other isolated from a buffalo, that cluster with a recently proposed novel pestivirus species.

Animals↗
PubMed2005

Neurons in monkey visual cortex detect lines defined by coherent motion of dots.

Form perception from coherent motion is an important aspect of vision. Representations of one-, two- and three-dimensional forms have been found at various stages of cortical processing using random-dot stimuli, whereas representations of biological objects like a walking human being concentrate at higher stages of processing. The perception of biological objects can be induced by sparse dot stimuli that consist of a few dots that mark the joints of the human body [G. Johansson (1973) Percept. Psychophys., 14, 201-211]. In the present study, we aimed to investigate whether neurons in early visual areas that respond to bars and edges defined by luminance contrast also signal bar-like objects from sparse dot stimuli. We studied single neurons with rows of 3-24 dots that were either collinear or scattered within a rectangular form. These dots were moved coherently on a uniform or dotted background, and human observers perceived them as rigid rods or other bar-like objects. We found neurons in the visual cortex of the awake, behaving monkey that responded to these stimuli and were sensitive to the orientation of these objects as for conventional bars or edges. Stimulus conditions that failed to induce these percepts in human observers also evoked weaker responses or none in these neurons. We found these neurons with increasing frequency in areas V1, V2 and V3/V3A. The results suggest that the visual cortex not only detects biological objects, but also lines and other bar-like objects from sparse dot stimuli, and that this function evolves at an early stage of processing.

Animals↗
PubMed2004

Efficacy of oral vaccination in the final stage of fox rabies elimination in Switzerland.

Subsequent to rabies vaccination campaigns, two well-established methods for the determination of the proportion of vaccinated foxes--the detection of tetracycline (TC) in bones and the detection of virus neutralizing antibodies (VNA) in thoracic fluids--were used and compared. Special emphasis was given to the effect of a new method of bait distribution at the den, which is primarily targeted at young foxes. The overall proportion of vaccinated animals estimated by TC was 60% as compared to 50% by VNA. In young foxes overall, significantly lower proportions of vaccinated animals (58% by TC and 40% by VNA) than in adult foxes (75 and 59%) were estimated with both methods. Low proportions of vaccinated young animals were found after spring (39 and 18%), but also after autumn vaccination (56 and 35%). In contrast, after den vaccination the level of vaccination of young foxes reached that of adult foxes. The theoretical implication of the successful elimination of fox rabies in Switzerland in spite of a relatively low overall proportion of VNA-positive animals is discussed.

Administration, Oral↗
PubMed2002

[Border disease in a flock of sheep].

This report describes border disease in a flock of sheep in Switzerland. In April 2001, three ewes in a flock of 41 sheep gave birth to lambs that had generalized tremors and excessively hairy fleece. One of these, a three-week-old female lamb, was referred to our clinic for further diagnostic work-up. The lamb was very nervous, bleated constantly and had generalized muscle tremors, which were more pronounced in the head region. Hind end ataxia was observed, and the lamb was slow to correct its posture when the hind limbs were abducted, adducted or crossed. Blood samples were collected every six weeks to determine antibody titres to pestivirus and for virus isolation via cell culture. A skin biopsy sample was also collected and examined immunohistochemically for pestivirus antigen. Antibody titres in the first tests were suspicious and those of the second were negative. Pestivirus was identified in cell culture, and the skin biopsy sample was positive for pestivirus antigen. Blood samples were collected from all of the ewes and lambs and the buck for virus isolation via cell culture and determination of pestivirus antibody titres. Thirty-one animals were seropositive, six had borderline antibody titres and four were seronegative. Pestivirus was isolated from eight animals, which included the lamb described in this report. Of the virus-positive animals, three were seronegative, three others had borderline titres and two were seropositive. Six of the eight viruses isolated from cell culture were further characterized genetically via retrotranscription and polymerase chain reaction and subsequent sequencing. The phylogenetic analysis revealed that the causative agent was border disease virus. This is the first time that border disease virus has been isolated in Switzerland. The lamb referred to our clinic was observed for three months; it was then euthanatised and a postmortem examination was performed. Immunohistochemical examination of numerous organs revealed pestivirus antigen. The source of infection was though to be infected sheep from another flock, which shared a pasture. All antigen-positive animals were slaughtered.

Animals↗
PubMed2001

Phylogenetic analysis of small ruminant lentiviruses from Southern Brazil.

The first lentivirus isolated from sheep in Brazil was analysed phylogenetically. Evolutionary trees of the proviral 597 nucleotide gag and 432 nucleotide pol sequences obtained by the maximum likelihood method demonstrated that the sheep isolate clustered with prototype Maedi Visna virus whereas three lentiviruses isolated from goats in the same geographic region were close to caprine arthritis encephalitis prototypes. A subsequent comparison of sequence data of these viruses with those contained in the EMBL sequence database revealed that, in contrast to caprine prototypic viruses, all prototypic Maedi Visna viruses contain a deletion of six nucleotides in the gag gene resulting in the deletion of two residues in the central region of capsid protein. This deletion may be a useful marker in the analysis of small ruminant lentiviruses, especially when considering possible transmission of lentiviruses between sheep and goats.

Amino Acid Sequence↗
PubMed2001

The effect of infection with bovine viral diarrhea virus on the fertility of Swiss dairy cattle.

Bovine viral diarrhea virus is a major cattle pathogen with a worldwide distribution. Animals may be infected with BVD virus transiently or persistently. Transient infection leads to protective immunity. Persistent infection is unique because it is associated with an immunotolerance that is specific to the infecting strain of BVD virus. Persistent infection results from viral invasion of fetuses between the second and fourth month of development. Such animals are of prime importance in the epidemiology of BVD because they shed large amounts of virus, and thus serve as a constant source of infection for non-immune animals. Infection of pregnant animals during the first two months of gestation may result in an increased rate of return to estrus. Animals infected in the period of five months to birth may abort or give birth to calves with malformations. The effects of BVD virus on fertility and gestation are well documented from experimental infection. However, much less is known of the extent of losses under field conditions. The main reason for this may be the multitude of other causes of increased return rates and gestation failures. In addition, the incidence of infection with BVD virus may vary over time and depends on management practices. In this study, we investigated the impact of BVD virus on gestation failures under field conditions in a large cattle-breeding area of Switzerland, where no specific measures to control BVD are in effect. Our approach consisted of relating seroconversions to BVD virus with the rate of return to estrus, abortion, and birth of calves with apparent malformations. These parameters of fertility were compared to those of animals immune to BVDV infection due to previous exposure to the virus and animals without seroconversion. Our data show that infection with BVD virus during the first 45 days of gestation did not influence the rate of return to estrus. By contrast, we observed a statistically significant increase in the abortion rate in mid-term gestation (Days 46 to 210) while no such effect was observed in the later stages of gestation. No clinically manifest malformations were observed in the offspring of animals that had seroconverted to BVD virus. In our study population the prevalence of BVDV antibody positive cattle varied only slightly between 78% and 80% over the period of observation. Our data showed that 7% (CI: 2.4-14%) of fetal deaths may be attributable to infection with BVD virus.

Animals↗
PubMed2001

Noncytopathic bovine viral diarrhea virus inhibits double-stranded RNA-induced apoptosis and interferon synthesis.

Bovine viral diarrhea virus (BVDV), a pestivirus of the Flaviviridae family, is an economically important cattle pathogen with a worldwide distribution. Both noncytopathic (ncp) and cytopathic (cp) biotypes of BVDV can be isolated from persistently infected cattle suffering from the lethal mucosal disease. The cp biotype correlates with the production of the NS3 nonstructural protein, which in the corresponding ncp biotype is present in its uncleaved form, NS23. Previously, we have shown that cp but not ncp BVDV induces the formation of alpha/beta interferons in bovine macrophages. In this study, we demonstrate that ncp BVDV inhibits the induction of apoptosis and the expression of interferon alpha/beta by poly(IC), a synthetic double-stranded RNA (dsRNA). Inhibition was observed only in cells which had been infected with ncp BVDV at least 12 h prior to the addition of dsRNA, which indicates that expression of viral proteins is necessary for the ncp virus to inhibit the effects of poly(IC). Additional experiments using transfected poly(IC) showed that ncp BVDV interfered with the intracellular action of dsRNA rather than with its uptake into the cells. Infected cells were not resistant to induction of apoptosis by actinomycin D or staurosporine, which suggests that ncp BVDV may specifically interfere with signaling through dsRNA. Interference with the innate antiviral host responses may explain the successful establishment of persistent infection by ncp BVDV in fetuses early in their development.

Animals↗
PubMed2000

Prevalence of cattle infected with bovine viral diarrhoea virus in Switzerland.

A cross-sectional study was made in a major cattle-breeding area of Switzerland to investigate the prevalence and local distribution of animals antibody positive to bovine viral diarrhoea (BVD) virus and of persistently infected animals. The sample size and statistical analysis took into account the possible clustering of persistently infected animals on individual farms. Of 3440 animals tested on 121 farms, 1982 were found to have antibodies to BVD virus (95 per cent confidence interval for the population prevalence: 57.6+/-4.5 per cent) and 22 were persistently infected (estimate for the population prevalence: 0.64+/-0.34 per cent). The detection of persistent infection in animals less than seven months old was improved either by retesting one year later, by using an antigen-capture ELISA or, in selected cases, by the analysis of original serum samples by reverse-transcription PCR. The results showed that the prevalence of persistent infection may be underestimated by as much as one-third when antigen detection alone is used. None of the 121 farms investigated was free of antibody-positive animals and one in eight herds had at least one animal that was persistently infected. The prevalence of antibodies was lowest in seven- to 12-month-old animals (22.9 per cent) and highest in animals aged five years or over (84.9 per cent).

Animals↗
PubMed2000

The detection of proviral DNA by semi-nested polymerase chain reaction and phylogenetic analysis of Czech Maedi-Visna isolates based on gag gene sequences.

A semi-nested polymerase chain reaction (snPCR) for detecting proviral DNA of ovine lentivirus (OvLV) in peripheral blood mononuclear cells was developed. Primers for snPCR were situated within the gag gene of the Maedi-Visna virus (MVV) genome. A comparison between the snPCR and serological tests (agar gel immunodiffusion test, immunoblot) were performed using 98 ovine blood samples. Thirty (30.6%) of the 98 sheep examined had antibodies specific for the MVV. PCR showed 21 of them to be positive and nine seropositive animals to be PCR negative. Six of the 68 serologically negative sheep were found to be PCR positive, probably due to delayed seroconversion. The PCR amplification products of these six sheep were sequenced and subjected to phylogenetic analysis. The resulting phylogenetic tree of partial gag gene sequences confirmed that the ovine lentivirus genotype in the Czech Republic is more closely related to the prototype MVV isolates than to the caprine arthritis encephalitis viruses.

Animals↗
PubMed2000

Anatomy and physiology of a neural mechanism defining depth order and contrast polarity at illusory contours.

We studied the anatomy and physiology of neurons in monkey visual cortex, which contribute to mechanisms segregating figure and ground at contours based on information provided by occlusion cues. First, we defined the location of neurons sensitive to occluding (illusory) contours. These neurons were found most frequently in the pale cytochrome oxidase stripes of area V2 but rarely in V1. In area V2, they were found in all laminae and with similar frequencies. The few neurons recorded in area V1 concentrated in the upper laminae. Second, we studied the properties and anatomical location of neurons sensitive to occlusion cues (dark and light line-ends, corners). These neurons had end-stopped receptive fields and were found with similar frequencies in both areas. In area V1, they concentrated in the upper laminae. In area V2, they were found in all laminae and cytochrome oxidase stripes. These neurons responded to short stimuli of optimal length (bars, edges) and to stimuli terminating in their receptive field (line-ends, corners). Overall, about half of these neurons detected the direction of such terminations and about 60% were selective for certain types of termination. In summary, our results suggest that in monkey visual cortex, occlusion cues are represented in areas V1 and V2, whereas grouping mechanisms detecting occluding contours concentrate in area V2.

Animals↗
PubMed2000

Bovine viral diarrhoea virus and bovine herpesvirus-1 prime uninfected macrophages for lipopolysaccharide-triggered apoptosis by interferon-dependent and -independent pathways.

The flavivirus bovine viral diarrhoea (BVD) virus exists in two biotypes, cytopathic (cp) and non-cytopathic (ncp), defined by their effect on cultured cells. Cp BVD virus-infected cells undergo apoptosis and may promote apoptosis in uninfected cells by an indirect mechanism. Macrophages (Mφ) infected with cp, but not ncp, BVD virus release a factor(s) in the supernatant capable of priming uninfected Mφ for activation-induced apoptosis in response to lipopolysaccharide. A possible role of interferon (IFN) type I was suggested previously by the observation that this cytokine primed for activation-induced apoptosis and was present in supernatants of Mφ infected with cp, but not ncp, BVD virus. Here, supernatants of both Mφ infected with a wider range of cp BVD virus and Mφ infected with bovine herpesvirus-1 are shown to contain such priming activity. Two lines of evidence indicate that factors in addition to IFN type I prime uninfected Mφ for apoptosis. First, supernatants of Mφ infected with cp BVD virus contained much less IFN than is required for priming for apoptosis. Second, whereas antiviral activity was neutralized by a vaccinia virus-encoded IFN type I receptor, B18R, the capacity of the supernatant to prime for apoptosis was unaffected by this treatment. The apparent molecular mass of the factor(s) priming for apoptosis was between 30 and 100 kDa. Priming of uninfected cells for activation-induced apoptosis may add a new facet to virus pathogenesis and may contribute to the formation of lesions not related directly to virus replication.

Animals↗
PubMed2000

[Seroprevalence of maedi-visna and border disease in Switzerland].

3866 sheep from 226 flocks of breeding associations and 1218 sheep from 15 independent sheep owners were tested for the presence of serum antibodies against Maedi-Visna and Border Disease viruses. The flocks were randomly selected based on the relative proportion and the geographical distribution of the 4 predominant Swiss sheep breeds (Braunköpfiges Fleischschaf, Schwarzbraunes Berg- und Juraschaf, Walliser Schwarznasenschaf, Weisses Alpenschaf). Additionally two smaller breeds were included in the study (Charollais Suisse, Milchschafe). Sera of all sheep older than 1 year were collected together with data characterizing host and management factors. The sera were tested using established ELISAs for detection of antibodies to Maedi-Visna and Bovine Virus Diarrhea/Border Disease viruses. ELISA results of Maedi-Visna serology were confirmed by immunoblotting. 9% of the sheep of breeding associations were antibody-positive for Maedi-Visna virus. The results of the different breeds varied between 0.4% and 36%. A multiple logistic regression procedure identified breed, age, airing in barns, herd size, pasturing on alps and way of keeping the animals during winter as associated factors with individual serostatus. The prevalence of antibodies to Border Disease was 20% in sheep of breeding associations and 65% in those of independent sheep owners.

Animals↗
PubMed2000

[Pilot project for eradicating maedi-visna in Walliser blacknose sheep].

Maedi-Visna is a lentiviral disease of sheep with a worldwide distribution. The transmission of the virus occurs primarily via colostrum and milk from the infected ewe to its newborn lamb but also horizontally between sheep. The most obvious clinical symptoms are progressive dyspnea and emaciation. In this prospective study an eradication based on serological testing and removing of seropositive animals was performed in 24 flocks of sheep of the breed "Walliser Schwarznasenschafe" leading to a reduction of the seroprevalence from 36% to 1% within two years. The control group consisted of 21 flocks of sheep. Lambs of seropositive ewes had a 7.6 times higher risk to seroconvert within their first two years of life compared to those of seronegative ewes. The dynamics of the spread of the infection were studied in birth cohort groups. Cohort animals of seropositive ewes showed an obvious trend to seroconvert slowly. Seropositive ewes had a significantly lower reproduction rate and their lambs suffered from significantly higher death and lower growth rates, probably due to a reduced milk production, resulting in economic losses.

Animals↗
PubMed1999

How to succeed as a virus: strategies for dealing with the immune system.

Viruses may be viewed as genetic information whose success depends on avoiding elimination from individual hosts, or, if this is not possible, in persisting in the population of their hosts. The immune system represents the crucial defense mechanism responsible for the elimination of viruses from individual hosts and for the establishment of immunity that prevents a recurring infection by the same virus. Herd immunity, i.e., immunity of the population against infection resulting from the immunity of a certain fraction of the individuals of the population, represents an important concept in the interaction of viruses with their hosts. Thus, if the number of susceptible hosts decreases below a critical threshold, viruses may risk extinction because they literally run out of substrate. This possibility is increased due to the viruses' low resistance to inactivation outside their hosts by physical influences, such as heat and ultraviolet radiation. Some viruses have adopted a strategy of dual host tropism, i.e., they may reside in reservoir hosts that permit them to survive for extended periods of times. Examples of such viruses are the large and taxonomically diverse group of arboviruses. Moreover, although not normally discussed under this aspect, influenza viruses can also be said to have adopted this strategy, in view of water fowl representing reservoir hosts from which complete viruses may directly cross over to mammals, as was the case with the equine Jilin (Guo et al., 1995) or, more recently, the H5 subtype of influenza virus in humans (Shortridge et al., 1998). In addition, influenza viruses of birds may be transmitted, albeit only partially, through genetic reassortment (Shu et al., 1996).

Animals↗